Interphase fluorescence in situ hybridization and spectral karyotyping reveals hidden genetic aberrations in children with acute lymphoblastic leukaemia and a normal banded karyotype

Twenty-two cases of childhood acute lymphoblastic leukaemia (ALL) with norm al G- or Q-banded karyotypes were studied by interphase fluorescence in sit u hybridization (FISH) and spectral karyotyping. Probes detecting MLL, BCR/ ABL and TEL/AML1 rearrangements were used for the interphase studies, along with centromere-specific probes from chromosomes 17 and X. In 10 patients (45%), previously undetected aberrations were demonstrable. Specific gene r earrangements and structural changes were found in six cases and numerical changes in five. Five of these aberrations have previously been reported to have an impact on prognosis. Three cases were massively hyperdiploid and, in one, the prognostically important BCR/ABL fusion was detected. In additi on, a near-haploid karyotype with 27 chromosomes was found in one patient a nd TEL/AML1 rearrangements were detected in two cases. This study indicates that about half of childhood ALL cases with apparently normal karyotypes h arbour genetic aberrations that may be detected using interphase FISH and s pectral karyotyping.